PROJECT SUMMARY/ABSTRACT North America?s opioid epidemic is a major driver of morbidity and mortality, with opioid-related overdoses becoming the leading cause of accidental death and opioid injecting driving HIV and hepatitis C (HCV) outbreaks. To date, there has been a lack of research into individual and extra-individual influences on the implementation and effectiveness of comprehensive and innovative responses to the opioid epidemic. As a consequence, there is a lack of understanding regarding how to optimize the response to the opioid epidemic, as well as the combination of interventions that are most effective in reducing opioid-related harms. Based in Vancouver, Canada, the proposed research will employ an innovative ethno-epidemiological approach to explore: (1) the implementation of innovative and comprehensive opioid-focused interventions and their impact on opioid-related outcomes; (2) the impact of the integration of evidence-based practices in the management of opioid use disorders (OUD) across the continuum of care on addiction treatment outcomes; and, (3) social, structural, and environmental influences on access to and retention in evidence-based treatment, and the onward impact on opioid-related outcomes. As the site of one of North America?s most comprehensive responses to the opioid epidemic, Vancouver is the ideal setting to undertake the proposed research. Vancouver has implemented innovative opioid-focused interventions that are currently being considered ? but are not yet available ? elsewhere in the US and Canada, including: supervised injection services; low-threshold opioid agonist therapies; opioid maintenance therapy; and, fentanyl-based drug checking and monitoring services. Additionally, locally-developed clinical practice guidelines for the management of OUD (recently profiled in JAMA) are being implemented across acute, residential, and community care settings alongside other changes to the healthcare system, including the systematic integration of opioid-focused treatment and harm reduction programming into hospital settings. The proposed study will be nested within the research infrastructure of the British Columbia Centre for Excellence in HIV/AIDS, which includes three NIDA-funded, longitudinal cohort studies that include opioid-using PWUD (HIV-negative and HIV-positive) and drug-using street-involved youth (SY) and are linked to external health and spatial data. Thus, this approach offers a ?value-added? opportunity to harness these cohort studies to undertake epidemiologically and spatially-informed sampling and targeted recruitment of PWUD and SY and collect qualitative data that can be triangulated with cohort-based and external data. Extending our ethno- epidemiological research to examine this comprehensive response to the opioid epidemic will result in a more complete understanding of influences on opioid-focused interventions than is possible through epidemiological research alone. The proposed research is aligned with the NIDA Strategic Plan (2016-2021), and will generate evidence that will be critical to informing the optimization and scale-up of the response to the opioid epidemic.